Summary
Platelet-mediated thrombosis is a dreaded clinical event and is the primary cause
of acute coronary syndromes and post-percutaneous intervention (PCI) ischaemic events.
There has been a long standing interest in the ex vivo quantification of platelet reactivity to assess the risk of thrombosis. Early studies
demonstrated platelet activation and heightened platelet reactivity in acute coronary
syndromes and after PCI. However, a demonstration that heightened reactivity actually
precipitated the ischaemic event was lacking. Our knowledge of platelet receptor physiology
and the advent of novel inhibitors have significantly advanced the field. The P2Y12 receptor has been shown to play a pivotal role in the amplification of platelet activation
by multiple agonists and its inhibition has resulted in improved clinical outcomes.
The most widely used drug to block P2Y12 receptor, clopidogrel is associated with resistance in selected patients and these
patients have been shown to be at increased risk for post-PCI ischaemic event occurrence
in multiple studies. Importantly, a threshold of high platelet reactivity has been
demonstrated, and beyond this threshold ischaemic events occur precipitously. Based
on the current evidence, it is rational to quantify the intensity of the ADP-P2Y12 interaction in the patient at the greatest risk for thrombosis-the PCI patient. However,
there is only evidence from small clinical trials demonstrating the clinical efficacy
of changing an antiplatelet regimen based on an ex vivo platelet function measurement.
Moreover, there are numerous patients with vulnerable coronary anatomy that have not
yet experienced plaque rupture; the prognostic role of a measurement of platelet reactivity
in the latter group has never been studied. Large-scale trials are ongoing that will
investigate the role of personalised antiplatelet therapy in the PCI patient.
keywords
ADP receptors - atherothrombosis - clinical trials - antiplatelet drugs
